Since first approved for use in dogs by the FDA in 2009, trilostane (Vetoryl) has become a popular drug commonly used for treatment of dogs with hyperadrenocorticism (Cushing’s syndrome) (1,2). Trilostane is a synthetic nonhormonal steroid analog that acts to inhibit the adrenocortical enzyme 3-beta-hydroxysteroid dehydrogenase, as well as 11-beta hydroylase. By blocking these adrenocortical enzymes, trilostane acts to actively interfere with the adrenal’s metabolic pathways and decreases the synthesis of the adrenal end products, including both cortisol and aldosterone (1-3).

Currently, the initial dosage of trilostane recommended by the manufacturer ranges 2.2-6.7 mg/kg, given orally once each day. However, it is clear that the duration of adrenal inhibition in most dogs is much less than 24 hours (1,4,5), and a number of adverse reactions can develop secondary to the drug, especially if higher doses are given (6-12).

Because it is known that trilostane generally has a duration of effect that is less than 24 hours, further investigation of a twice daily dosing regimen is warranted. Dividing the daily dose into twice daily administration might also help lower the prevalence of adverse effects associated with the drug. The purpose of this current study by Feldman (13) was to carefully evaluate the effects of twice-daily, lower-dose trilostane treatment administered to dogs with naturally occurring Cushing’s syndrome.

Objective—To evaluate effectiveness and incidence of adverse reactions to twice-daily lower-dose oral administration of trilostane in the treatment of dogs with naturally occurring hyperadrenocorticism.

Design—Clinical trial.

Animals—47 dogs with naturally occurring hyperadrenocorticism.

Procedures—47 dogs were treated orally with trilostane (0.21 to 1.1 mg/kg, q 12 h). All dogs were reevaluated at 2 weeks and 2 months, 38 dogs at 6 months, and 28 dogs at 1 year of treatment.

Thirty-eight dogs had pituitary-dependent hyperadrenocorticism (PDH); 15 dogs did not require a dose increase during the study, and at each of 4 reevaluations, 10 of 15, 13 of 15, 14 of 15, and 11 of 11 had a good response. Twenty-three dogs with PDH had their dose or frequency of trilostane administration increased during the study.

Mean trilostane dosage at 1-year reevaluation in dogs with a good response was 1.7 mg/kg (0.8 mg/lb), twice daily, or 1.1 mg/kg, 3 times daily. At each of 4 reevaluations, 17 of 23, 14 of 23, 17 of 23, and 13 of 17 dogs with PDH had a good response. Five dogs became ill because of trilostane-induced adverse effects, but only 1 required hospitalization.

Conclusions and Clinical Relevance—Administration of initial lower doses of trilostane to dogs with hyperadrenocorticism is effective.

Bottom Line:

Initial daily dosage of trilostane
When this drug was first used in Europe over a decade ago, the original starting dose was 4-10 mg/kg/day (7-12). However, as experience with the drug grew, it became apparent that these doses were too high in many dogs and lower doses were needed. Accordingly, the dosing recommendation on the US package insert states that an initial daily dose of 2.2-6.7 mg/kg is recommended (4).

My recommended starting dose is either 2 mg/kg given once daily or 1 mg/kg given twice daily. This is similar to the doses used in this study by Feldman (13), where the mean trilostane dose administered to his dogs was 0.86 mg/kg, twice daily (or a mean total daily dose of 1.72 mg/kg). Like Feldman, I feel that it is best to start with a daily dose that is at the low end or even lower than that recommended in the package insert. I would never start a dog on a dose at the higher end of the recommended dosage range (4-7 mg/kg), although some dogs with Cushing’s disease will eventually require daily doses that may be this high or even higher (1,14).

SID, BID, or TID administration?
Whether to start with once- or twice-daily trilostane administration is controversial (1,2). Although most dogs are controlled clinically with once-daily dosing, trilostane may begin to lose its effectiveness 8-10 hours after administration, so twice daily dosing may be necessary in a subset of dogs (1,4).

In addition, it is very possible that the efficacy of twice-daily dosing might be more effective than once-daily dosing in controlling the complications of Cushing’s syndrome (e.g., proteinuria or hypertension). However, the answer that question remains unclear (15), and additional studies are needed to resolve that issue.

So what do I recommend? Until it is proven that SID or BID treatment is better, I prefer to start with a twice-daily regimen —if feasible and the owner agrees —because controlling cortisol concentrations throughout as much of the day as possible makes sense to me. In diabetic dogs with concurrent Cushing’s disease, twice-daily administration is essential in avoiding large fluctuations in serum cortisol concentrations during the day (1,2). With once-daily trilostane administration, adequate diabetic control will be next to impossible in many dogs with concurrent Cushing's syndrome.

What about TID administration? In this study, 9 (24%) of the 38 dogs with PDH were eventually switched to a regime of trilostane, administered every 8 hours. In my practice, I have not found it necessary to use TID dosing, and I do not find that dose schedule very practical or realistic for most owners. If I can't remember to "take a pill" every 8 hours (and I can't!), how can we really expect the owners to give their dog a medication three times a day for the rest of their dog's life?

Monitoring & the goals of therapy
We must use a combination of the dog's clinical response and the results of ACTH stimulation testing to monitor dogs on trilostane treatment. In this paper (13), Feldman had three goals of therapy, which included the following:

Of these 3 goals, I agree completely with the last one — the owner's evaluation of the clinical response is key. As far as the urine specific gravity goes, I would agree that most dogs will be able to concentrate their urine to greater than 1.020 once the polyuria resolves. However, if the urine specific gravity is less than 1.020, I would certainly not raise the dose if the owner reported a good clinical response and serum cortisol concentrations were lowered to within the desired range.

Dosage adjustments — raising the dose
In this paper, Feldman recommends that dogs that continue to be symptomatic with a post-ACTH stimulation serum cortisol concentration > 5.5 μg/dl should have the daily dose of trilostane increased. I agree with that recommendation. However, the 5.5 μg/dl cutoff value used in his study was not very sensitive — 40 of the 122 dogs (or a third of cases of this report) with a good clinical response to trilostane had a post-ACTH serum cortisol concentrations higher than 5.5 μg/dl.

For my cases, I recommend maintaining a post-ACTH cortisol concentration between 2-7 μg/dl when tested 4-5 hours after the morning dose. So for a dog that was clinically improved but has a post-ACTH cortisol above 5.5 μg/dl but below 7.0 μg/dl, I would not recommend increasing the dose in those dogs. Many of those dogs will go on for months on the same dosage, without the need for a higher dose.

Dosage adjustments — lowering the dose
In this report (13), trilostane treatment was continued in dogs with a post-ACTH cortisol concentration less than 1.5 μg/dl, as long as no adverse clinical signs were reported. I disagree with that regime.

When using trilostane, it has become increasing clear that we do not want the cortisol values to drop too low, because that may indicate early or mild adrenal necrosis (1,11,12). In contrast to the protocol used in this reported study, I recommend stopping the drug in all dogs that develop a ACTH-stimulated cortisol values less than 2.0 μg/dl, and repeating the ACTH stimulation test in 1- to 2-weeks in those dogs. Some of these dogs will require that the drug be restarted at a lower dosage, but others will maintain low to normal serum cortisol concentrations for prolonged periods of time. And a subset of these dogs, presumably because of mild adrenal necrosis, will never need any further trilostane treatment to control the signs of Cushing's syndrome.

141 comments:

Would there be a concern if a dog has consistent pre stimulated cortisol less than <1, in this case between .7 and .9, but post stimulated cortisol between 3 and 5.5 ug/dl, with resolution of symptoms and no adverse signs of insufficient cortisol?

I wouldn't be overly concerned (unless there are adverse clinical signs), but I would recommend that you recheck another ACTH stimulation test in a month to ensure that the values don't fall any further.

Dr. Peterson, My dog is on 20mg of trilostane once a day. She is also a diabetic on insulin every 12 hrs. The pill I have now are 10mg. Her sugar seems to vary more than I would like, which I also check 2 a day. Do you think it be beneficial possibly to give the 10mg 2 a day also, instead of the whole 20mg in the morning?

Just checking back in with an update. I split my trilostane does in 2, once (10mg)in the morning and once (10mg)in the evening for my diabetic/cushing terrier named Mia Cherry. After just one month, the change has been wonderful, sugar well regulated, and energy levels are even. I can't thank you enough for your advice Dr. Peterson. I knew in my heart to listen to you over my vet and I was right! Thank you for helping us save our animals. Debee & Mia Cherry

Hi. My beagel / Jack Russell mix was on Trilostane for 4 years, and did beautifully. She took 20 mg twice a day every single day and so many of her symptoms were reduced consderably! She lost her battle 4 days ago but I believe this Med gave her years of happiness. I have 53 20 mg pills that I would be happy to send to someone who is giving it. I know how expensive this drug is.Diane from Richmond, VA

Hi Diane, I sorry for your lost. My 10 year old lab has been dealing with Cushing for over 6 months. Some days are better than others. I currently live in Chesterfield Va if you still have your medications. Thanks. Oh what vet were you seeing.

I have a nearly 12 year old Weimaraner and two 7 year old Beagle sisters. One of the Beagles was diagnosed with Addison's disease in April and is now doing fine on Percorten-V and prednisolone. My weimaraner, Skye started vomiting and had intestinal problems about 3 weeks ago. After a few days, it had not resolved and I brought her to our vet. She had a cbc and results showed elevated liver enzymes. She began antibiotics and a supplement called Denamarin. She finished the antibiotics, responded well and seems healthy. She had an ultrasound to determine if she had any tumors - all her organs were normal. Skye then had the low dex testing for Cushing's and it was confirmed.

After some reading I realized that Skye had a few minor symptoms that I had attributed to normal aging in the past few months - dry coat, hind leg weakness, increased thirst, loss of muscle tone and a bit of a pot belly. Otherwise, Skye is 77 pounds, happy, active and alert. My vet has recommended starting Skye on an initial dose on vetoryl 120mg once daily for 7 - 10 days, then running the ACTH test. Depending on the results, she might then be cut back to 3 times per week. After reading about the side effects, I have concerns, especially since I have such recent experience with Addison's (and luckily my Dottie's crisis was not nearly as horrible as some.) As I believe that we are catching the Cushing's disease early, while Skye's symptoms are minimal - Would you suggest a lower dose protocol for Skye?

My goal is to keep my dogs as happy and healthy as possible for as long as I can, but I admit that my vet bills for testing and meds are overwhelming.

Dr. Peterson, this has been a ost helpful blog. My 12 year old female shephard was diagnosed about 9 months ago with Cushings and has been on 90, then 60 and now 30 mgs of Vetoryl for the past few months. She also takes Soloxine BID. Now she has elevated liver enzymes, (really through the roof) including the BA. Ultrasound showed not abnormality in the liver. Can longer term use of Vetoryl cause elevated liver values? She just started Denanmarin and I believe the vet may suggest Ursodiol as well, along with a lower protein diet. Thank you.

Dr. Peterson, my dog is 16lbs and was taking Trilo 10mg 2x/day for 3 months then vomited. Stopped Trilo for 36hrs and ACTH stim showed pre 2.4 post 10 ug/dL. Has been off Trilo for 2 1/2 wks. During this time PU/PD, hunger, lack of energy has shown up. ACTH stim retested showed pre 10 and post 18 ug/dL. Our vet wants to restart Trilo at 5mg 2x/day. Is this the right course of action? Thank you for any advice.

Thank you for responding. He did have an ACTH 2 weeks prior to vomiting 2 days in a row which was pre 0.9 post 2.3 ug/dL. He did have a resting cortisol test the day after stopping which was low and our vet wanted to stop the Trilo.

My 13 year old 12 pound female Cockapoo has recently been diagnosed with Cushings and has been on 10 mg Vetoryl once a day. (She also has had hypothyroidism for 12 years and is on soloxine). She had an ACTH stimulation test after 13 days and the post stimulated cortisol was 17. Her vet wants to increase her dose to 10 mg twice a day. Does Vetoryl take time to reach its full effectiveness? Should we increase the dose now or wait until a repeat ACTH in two more weeks. I am concerned about side effects from doubling the dose.

My 9yr old dog with Cushings has 7mm spleen nodule seen by ultrasound. Splenectomy is recommended to prevent future problem and do check for cancer. Cushings is currently under control with Trilostane. Are there unusual risks for this surgery with Cushings?

Thank you for keeping your blog up-to-date with a vast amount of information. I have a question regarding the once daily or bid dosing. I plan to start my dog on trilostane. She weighs 11.3kg. The closest pre-made capsule is 30mg (would equate to 2.65mg/kg/d). I am considering compounding the capsule myself. (I am a pharmacist.) I see in your blog that in doing trilostane, you recommend 2mg/kg/d or 1mg/kg q 12h. When I read the package insert for Vetoryl, it states to go from once daily to twice daily dosing, a dose increase by 1/3 to 1/2 is recommended. Do you agree with this practice or apply this to your own practice? Your insight is appreciated.

My question is similar to others here: Is prolonged use of Trilostane correlated with elevated liver enzymes?

My dog's details are below, but her most recent lab tests showed sky-high liver enzymes. We dechallenged Trilostane for 4 days and re-started it a couple of days ago. We don't have unlimited money, so we didn't get a chemistry re-test while she was off Trilostane, but I'm wondering if others have experienced this.

Dear Dr Peterson, As an expert in the field of Veterinary Endocrinology I was hoping you may be able to give me a little advice or comment on my 8 1/2 year old Dogue de Bordeaux's Cushings diagnosis.

She is a big girl at just over 64KG (142 lbs) and has been taking Veroryl for 6 weeks now. She started on 90mg per day but was later reduced to 60mg due to problems with her hind legs. The latest ACTH test suggests she is doing well (basal - 44 nmol/l, post - 93 nmol/l), Liver and cholesterol are still high but have improved. However, she is still lethargic and is the same weight even though we are feeding her around 25% less now.

Given she is on such a low dose for her size which seems to be controlling the cortisol production, could that indicate some other underlying issue or simply that the tumor is extremely small ?

I know you are very busy and may not be able to respond but any insight or advice would be very much appreciated.

My dog, a 34.5kg 10.5 year old female Rhodesian Ridgeback, has just been diagnosed with Cushing's disease and has been prescribed 60mg Vetoryl once daily (to be taken in the morning with food) and I am now wondering whether she should start on a twice daily administration?

Her bloods indicated that she had raised ALP at 1700 and an ACTH confirmed Cushing's.

The vet believes her Cushing's disease has occurred due to prolonged use of prednisolone some years ago, when she had an autoimmune problem which affected her joints after a suspected tick bite. She has had a pot belly, ravenous appetite, muscle wastage and frequent urination since this time (before prednisolone she had a poor appetite). Additionally, she began to grow excessive hair on her sides at the rear, near her leg crease, maybe 2 years ago, but the vet didn't see anything wrong then. I have read about hair loss in Cushing's disease, but not hair gain - is this something you have come across?

After reading your blog and other information on the web, I am now concerned that a fast reduction in the amount of cortisol may induce her previous joint problem, which prevented her from moving when at its worst. Would it be better to start her off on a split dose in your opinion?

Also, do you have to administer Vetoryl at the exact same time each day?

It sounds like your dog may have iatrogenic Cushing's disease, induced by chronic or excessive administration of the prednisone. If this is indeed the case, trilostane would not be helpful. In fact, administration of the drug would be contraindicated. Talk to your vet about how the diagnosis was made and to confirm that you dog has spontaneous Cushing's syndrome due to either bilateral adrenal hyperplasia or a unilateral adrenal tumor. I'm assuming that an abdominal ultrasound was done to confirm these latter findings but again, you need to consult with your vet (or get another opinion).

Dr. Peterson, I have an almost 11 year old boston terrier. She was diagnosed with Cushings a little over one month ago. She has been on Vetoryl for 31 days. She is prescribed 30 mg once daily (I give it to her with breakfast), she is 28-29 lbs, normal weight 26-27 (before her ravenous appetite began about 6 months ago). Her initial tests 10-14 days after beginning the medication showed that she was in the normal range. However, in the past week her increased thirst, urination and now hunger returned. She even peed the bed one night:(. My vet did a UA this morning and the results were normal. She recommended that I give her a second dose of the 30 mg. 8 or so hours after the first. Do you agree with this treatment or should her 30 mg dose be split? Also, I give it to her with her breakfast, but sometimes she has it before she eats, would you suggest giving it to her after? Could that make a difference? Thank you so much, Samantha

Dr. Peterson, This blog has been so helpful. I have an 11.5 year old male neutered min pin who weighs 18.6 lbs. His cushings was diagnosed 12 months ago with an acth stim test post corstisol sample of 34 (after a full blood screen with high alk phospates). In hindsight he probably had cushings for 2 years earlier as he was given up to the shelter where we got him and was there for some time with the same symptoms that led to the cushings diagnosis (frequent water drinking and urination, ravenous appetite, panting, pot belly). He has been on vetoryl 10mg once daily dosing for the past 12 months. His post acth samples have been 14, 12, 12 and 10.4. The recent test (pre: 3.3 / post 10.4) was done last week. We have seen some improvement in terms of drinking and urination lessening (used to urinate 10 times a day and now goes 6-7), however his ravenous eating has not improved and he still has such weakness in his hind legs. Do you think it is safe to raise the dose? Our vet feels he might crash but the vetoryl insert says he should be on a higher dose and quite simply the dog still suffers so much from the same cushings symptoms despite a full 12 months on the same dose and the improved post cortisol sample. He is also on fluoxetine 15mg (we may raise it to 20mg) once a day for anxiety (he was abused by previous owners and attacked by other dogs - both before being with us). Any advice would be so appreciated. Thank you

Dr Peterson, My Maltese has just been diagnosed with Cushings. She weighs 16 lbs. I have recently read that Vetoryl has a 5 mg capsule. What do you think concerning starting dose and once or twice a day? I see where average dosing is 1mg/kg which would be approx 7.27 mg. Just wanting to pick your brain...

Good Morning Dr. Peterson, My 8 year old Maltese, Mimi, just had her ACTH stim test. Her Pre # was 2.5 and her Post # was 25.1. She previously took the Low dose Dex: Her Base was 8.4; Her 4 hr. was 0.6 and 8 hr. was 1.3. Vet said Dex test wasn't conclusive but ACTH was. What is your opinion ?

Dr Peterson my Border Terrier has been diagnosed with Cushings and has been on 30mg of Vetoryl for almost two weeks but has lost her appetite. An ACTH stimulation test was done 3 days ago and the results were good so the vet was reluctant to stop the dosage, I have read the article re twice a day dosage and wonder if that would be a better option for her and also wonder if her appetite would return to normal.

Thanks for your response I have tried all sorts of foods to tempt her to eat but she is only having a tiny amount of beef to get her tablet down & maybe 2-3 biscuit treats but she is not showing any other signs of being unwell. Prior to starting the treatment she was eating one meal a day I think maybe trying twice daily medication to reduce the side effects may be the way forward. Any suggestions on getting her to eat would be gratefully received.

My 13 year old part Pomeranian has been taking Vetoryl 60 mg daily for about a year for Cushings. It controlled the excessive thirst and urinating in the house. In June he started licking at an itchy rash to both groins constantly. My vet has tried 3 different antibiotics, an anti-fungal with shampoo and a hypoallergenic diet. It keeps getting worse. Recently I thought he has maybe developed a sensitivity to the drug so I stopped it and it has improved somewhat. Has anyone else experienced this?

Dr. Peterson, I just wanted to Thank-you for the information you shared with me about my Maltese, Mimi. She weighs 16 lbs and has cushings. She is currently taking Vetoryl 5mg twice a day and it is working beautifully. In 14 days her pre test numbers have dropped from 2.5 to 0.3. Her post test has dropped from 25.1 to 10.7. Most of all she is more comfortable. I just wanted to THANK-YOU for your insight and knowledge. You are spot on and you are doing a great service to all of our loving pets and they THANK-YOU as well !!!!! We started her on 5mg once daily but her symptoms crept back around the 10-12 hour mark. The half life is definitely short. When we upped her dose to 5mg twice daily, she improved significantly. Point Taken.

Dr. Peterson, Mimi has been on Vetoryl for about 6 weeks ( 5mg twice a day) She weighs 17 lbs. We have checked her ACTH recently. She was 2.6 Pre test and 9.7 post. She has still been extremely thirsty and urinating frequently and panting a lot at night. My Vet wants to increase to 10 mg twice daily and re-test stim in 14 days. What is your take on the increase ?

We're having a hard time getting to correct dosage of vetoryl. We started at 5mg twice daily, we're at 10 mg twice daily. She is 17 lbs. Last Acth test showed she had actually gone up from 10.3 to 13 in post test numbers. We also found her glucose numbers were 480. They have been in range before now. Dr put her on versulin twice daily for diabetes and we're contemplating going to 15 mg twice daily of vetoryl. I'm not sure that will even be enough. At her weight and now with diabetes, what may be the high end on vetoryl dosage. I don't want to switch to lysodren yet because she is tolerating the vetoryl well. We just need to get to a proper dosage a soon as possible. Would like to hear your thoughts. Thanks, Randy

Dr. Peterson-Greetings! I have a 17-1/2 year old Chihuahua recently diagnosed with Cushing's after we initially found his liver enzymes high before a scheduled dental cleaning. He currently weighs approximately 6.9 pounds, and my veterinarian wants to start him on 10mg once a day of Vetoryl capsules. After thoroughly reading your article, I would like to start Chico at 4mg twice a day, which seems reasonable to me, but then again, I am not a veterinarian, so I thought I would ask for your professional opinion if you would be so kind as to provide it. I have much more information with regard to the diagnostic tests that have been performed to reach the conclusion of Cushing's, but will forego them in this forum unless you ask for more information.Thanks very much for your consideration!Greg

Dr Peterson, I don't know idf my previous post went thru so I'm resending. My 15 lb maltese is currently on 15 mg vetoryl twice daily. I need to know if dogs go over the 3mg per pound upper amount is sometimes used. At present she is still at 13 post STIM test cortisol and she has developed diabetes just in past two weeks. We've been increasing slowly but I feel we need to move at at faster pace because the blood sugar is getting worse. Thus the reason to know high end mg for a 15 pound dog. I'm just guessing but I think she may need 25 to 30 mg twice daily. Her symptoms seem to be much worse at night. I'm afraid if we don't get to proper level it will become dangerous if not already. What is your insight???? When and would you consider switching to Lysodren ??? Thanks Randy

Dr Peterson, My Border Terrier Graham has stage 3 kidney failure, and also has Cushings which was diagnosed last June. He is sixteen years old and weighs 18 pounds. I understand that Vetoryl should not be given to dogs with kidney failure but when I mentioned this to my (previous) vet he said that we could give it to him and keep him carefully monitored. He had 10mg Vetoryl once daily for 6 weeks. His first ACTH after 2 weeks was pre - 5.25 post- 8.4, the second two weeks later was pre - 2.9 post - 8.9. Two weeks later I could see that he was not well and requested another ACTH. The result was pre 0.3 and post 3.4.The Vetoryl was stopped immediately and he has not been on it now for six months. For at least five months he showed no signs of Cushings but recently I have noticed that he is losing his coat and is drinking more..My new vet did another ACTH a few weeks ago, pre was 5.7 and post 25. Is there any Cushings treatment for dogs with kidney failure apart from Vetoryl? Many thanks for any advice you can offer, it is very much appreciated.

You could try doing a short (5-7 day) course of Lysodren to lower the levels. This could be extended to as many days as needed to bring the cortisol values down, as long as your dog tolerated it. Talk to you vet...

I'm assuming that your vet ruled out urinary tract infection as a predisposing factor for the kidney disease? Very common problem in Cushing's.

Dr.Peterson, my dog has been on vetoryl for 7 months. Recent post stim of 5.8 ug/dl. Symptoms controlled, minor incontinence unrelated to Cushing's. ALKP before starting vetoryl, 937 u/l, 4 months later 465, then 3 months later, 760. ALT increase from 126 to 174. What would cause this pattern? Is it the Cushing's or liver disease? Only other blood abnormality is CK- 219 u/l before vetoryl, After 4 months, 430. Ref. (10-200) Not sure if the CK is relevant since there wasn't another sample following the high result.

The reference range for the recent ALKP & ALT differs from the first two as they are pre anesthesia results. Thank you for your time.

If your vet suspects liver disease, an ultrasound with biopsy is recommended. You should be asking your vet what's the next step, or asking for a referral to a specialist if he or she doesn't know what to do next.

I have a 15 year old west highland terrier 17.75 pound just diagnosed 3 days ago with cushings vet put her on 30 mg twice daily been on 3 days presenting some lethargy not drinking not interested in eating her dry food but will take bites of steak beef etc. has developed bad dry cough with a choke like trying to get something out of her throat. Not drinking even when beef broth added to water. After reading this blog, I am going to split the dose to 1/2 30 mg capsule Twice daily. Has anyone seen a similar problem with the cough?

Dr. Peterson, I'm starting my 13lb Cushings mini poodle dog on 10mg of Vetoryl as per our vet. But I'm just terrified of her getting a life-threatening "adverse reacton" like adrenal necrosis/rupture. It says death can and has happened. Is there any extra monitoring that can be done to prevent an emergency/collapse/crisis? Does a lower starting dose reduce/eliminate the risk? Were the dogs that died in these studies given higher doses? And if my girl does well with the drug, is she out of the woods after a period of time or are these risks always going to be looming as long as she's on the drug? Thank you so, so much in advance.- Worried mama :(

This is a relatively safe drug and severe side effects are very, very uncommon. They are more common with higher doses. Talk to your vet about monitoring, which is essential in avoiding serious side effects.

Thank you so, so much. Vet just plans on doing the stimulation test after 10 days and seeing where to go from there. Hope that's the best we can do for her to make it as safe as possible. Thank you again.

With compounded product, you never know how potent the drug actually is, and it has been shown that the actual concentration can vary from batch to batch. I would always use the brand name product, if possible.

I belong to a canine cushing's forum and we have seen many dogs have that tremor/shivering, shaking thing going on and an ACTH stim test shows that their cortisol level is not low. Some dogs experience that tremor/shaky episodes after only a couple of doses of Trilostane, and this is with starting the dog at the 1mg per pound dosage of Trilostane. So if low cortisol is not the reason for the tremor/shakes/shivering, what else can it be?

Dr Peterson, I have a 10yrs Maltier 13.6kg with Cushings on 55mg once daily. She started on 30 but the tests and showed as well as other signs (panting) that she needed to move to the higher dose. She has tolerated well and is much improved and very happy with the professional care of her vet . The only problem is about a month after starting treatment she grits her teeth constantly making a crunching noise and after having her teeth checked and the vet speaking to a specialist know one can work our what is causing her to do this. I worry she is in some discomfort but seems to be happy and active. Can you shed any light on what this could be ? The vet had suggested moving to twice daily splits also as there is a a ball amount of panting going on in the evenings . Would this help with the gritting? Any help would be appreciated Thank you

Your dog's case is very complicated and I cannot really help by providing a sentence or two comment here. You need another opinion and workup to determine what to do, but a pituitary macrotumor may need to be excluded. I'd ask your vet for a referral to an internal medicine specialist.

Dear Dr Peterson, I am so glad to have found this page! I have a 9kg male bedlington terrier, Ullig, of probably around ten years old (we’ve had him for six years, he’d had several homes before that and no paperwork, he was supposed to be two when we got him but more likely four or so). He was diagnosed with Cushings a bit over a month ago - symptoms of thinning coat, slightly saggy belly, unusually hungry, drinking loads - I knew from a Bedlington terrier facebook group that they’re prone to cushings so took him to the vet for testing. The numbers are, pre-VetorylDiagnostic ACTH stim test cortisol pre ACTH 127.0 Nmol/L reference range 25.0 – 125.0 HIGHCortisol post ACTH 839 Nmol/L reference range 125.0 – 520 HIGH

Started Vetoryl 10mg a day for three days then 20mg a day (2x10mg with breakfast) for eleven days and had another ACTH stim test 5 hours after 20mg Vetoryl Cortisol pre ACTH 11.6 Nmol/L reference range 25.0 – 125.0 LOWCortisol post ACTH 161.0 Nmol/L reference range 125.0 – 520 The vet was happy with this and gave us a script for three months and to re-test then, but i’m a bit concerned about how low his baseline cortisol was, especially as he really does not like the vets and having his legs shaved for blood tests (I groom him myself and when i went to clipper his front legs last week he panicked, which is not usual for him) and so was likely to have been stressed when the sample was taken. We had a few days off the tablets because neither the vet or the pharmacy had 10mg tablets and he became quite symptomatic again, now its been another two weeks on 20mg in the morning and he’s sleeping for most of the day but drinking a lot in the late evening, so I’ve been thinking that it would surely make more sense to split the dose rather than have his cortisol levels falling so low and then getting high again by evening? Should he have the 10mg tablets 12 hours apart if so? Apart from the Cushings he’s not too bad, liver results are a bit high Before vetoryl Alkp 154 U/L, ALT 262 U/L , AMYL 365 U/L, Bile acid fasting 12.0 umol/L , Bile acid post fatty meal 58.1umol/L After two weeks of Vetoryl Alkp 154 U/L ALT 160 U/L Bile acid (not fasting) 19.5other bloods okay, no diabetes or thyroid problems. Thank you so much for you help, its already been enormously helpful to read something that backs up my thoughts!

Dr. Peterson, My Maltese that has been diagnosed with cushings and diabetes for the past 6 months has recently become blind. She is on 15mg vetoryl and 13 U vetsulin both twice daily. Symptoms are controlled. Is there any correlation with cushings and blindness. Was concerned with pituitary tumor and optic nerve. She is handling the situation well. What are your insights?

Almost all diabetic dogs eventually go blind from cataracts. That would be 10,000 times more common that a pituitary mass compressing the optic nerve! Talk to your vet.. if no cataracts, then do an MRI or CT.

Sorry for my ignorance. Mimi does have cataracts. Happened very quickly. Latest problem is we have to keep going up on vetsulin about every 2 months. She weighs 15 lbs and is currently on 13u vetsulin twice daily. Would other insulins possibly work better? What are the limit of units I can go up to of vetsulin. If she is insulin resistant, what can I do for her? I don't understand those specifics. Could you help me understand my options. ( 15mg vetoryl twice daily for cushing/controlled). I'm seeing vet about twice a month. Just trying to understand options, thanks. Randy

The main reason to tightly regulate diabetic dogs is to try to prevent development of cataracts. Unfortunately, this can be impossible in many dogs. Once cataracts have developed, you should regulate well enough to normalize body weight and thirst and not worry about being perfect anymore. It really doesn't matter because it's not going to prolong your dog's life or make her feel any better.

Dr Peterson,i see a lot of talk about splitting a dose. Our Vet prescribed 15 mg twice per day, but we could only get 30 mg capsules. As it says in the instructions 'do not open and split', can you please tell me if we can still open and Split (we bought empty capsules), or is there a reason for such warning.We are not pharmacists, the only things we can is open capsules and transfer part to empty one.Sorry for beginners question, but dont know what to do after reading instructions. Thank you Ana

You can do 10mg and a 5mg vetoryl or have compounded as Dr Peterson said. My dog uses 15mg as well and her Cortisol numbers are great. Her Diabetes is the biggest problem now. keep an eye on that. I used Diamondback for trilostane compounded with prescription.

Dr. Peterson, Could you tell me if some dogs respond better to Novolin NPH vs. Vetsulin ? Or any other Insulins? My doggie weighs 15.7 lbs and has currently been moved from 13 to 15u of vetsulin twice daily. Just curious what routes are possible from here. Thanks

You have been more help in solving an unsolvable problem than you will ever know. You have given me insight. Insight into questions we all must answer. My main concern is to make my pet, my friend, as comfortable as possible. Thanks for your vision and compassion. Randy

Our dog, a 12 year old Beagle, started with Vetoryl in November, 2015. At that time, he had thorough testing, including an ultrasound of his abdomen. Vetoryl was prescribed, and the results for the Cushing's were positive immediately, as his water consumption reduced, and he could sleep through the night. In May we took him to our vet for a well visit, and we mentioned his appetite was not as strong as it once was. Blood work was done, and our vet thought a visit to a specialist was warranted. Another ultrasound was done in early June, and cancer was found in his lymph nodes, spleen, kidneys, and liver. Our vet was astounded that this much cancer could appear so quickly. He died a week later. The only thing that changed was the addition of the Vetoryl to his daily routine. I have found nothing to indicate that this is a normal side affect of this medication, but it seems posible to me, and, if this is prescribed for other dogs, I would have a serious conversation with my vet about the potential for cancer.

I was hoping to gain your insight into my dogs case. A month ago he was diagnosed with cushings (16yr old Maltese X 8kg). The vet prescribed 30mg 2xday. My dog had adverse effects to Vetorly and became vague, shaking, loss of appetite and diarrhoea. The events that followed included fluids, prot X tabs and later death due to kidney failure. I guess my question is what do you make of this initial dosage of Vetoryl?

Thankyou so much Dr for your insight and fast response. It's truly a wonderful thing we are able to ask an expert in this field. I hope people read my post and take caution as my poor little Ferris suffered a great deal after taking Trilostane. Thanks again, Rachel

Hello, my 10.5 year old Boston Terrier was diagnosed with Cushing 2 weeks ago. He is taking 20 mg of vetoryl in the morning with food. He seems to have significant muscle wastage in his back legs and has difficult standing up and staying up. This started happening before we began the medication. His urination and food intake appear to be better. Once the medicine starts working, will he gain use of his legs again? How long will it take? Thank you for your time.

My 12 year old shar-pei mix has cushings. I am trying to wean him off chicken and rice that was started following surgery. He is taking Vetoryl 20mg in a.m. and 20 mg. p.m. His symptoms have returned after about a 2 week symptom free period. He started Wellness Core yesterday, had his first allergy shot since surgery, and started him again on Phycox.

Could any of these actions started the symptoms again. heavy panting, waking at night, and drinking excessive water. Thanks for your response.

Thanks Dr. Mark and Randy. My dog's symptoms started 3 years ago: heavy panting, skin abscess, hair loss, skin turned black on tummy, swollen mammary glands, pot-belly and hungry all the time. I asked the vet to do a Cushings test and it came back Cushings. Vetoryl was started in June. Most of the symptoms are gone, except the heaving panting has come back. He had surgery in June to remove a benign liver tumor. He had hydrocodone tablets left over so he's taking 2-3 tablets in order to sleep at night. I've read that dogs with Cushings have difficulty regulating their body temperatures. Outside temps are in the 90's so no more walks and brief time in the backyard. Avoiding the heat seemed to help a little yesterday, but he was still up last night heavy panting. His last ACTH was a "little low." I don't know what that means. I called my dog's vet yesterday and am waiting for the return call. My dog weighs 70 lbs. and is on 30 mg 2x a day. Thanks again for your comments.

My dog has missed 4 days of her Vetoryl because of delayed shipping to her vet's office. She was diagnosed with Cushing's disease several months ago and was responding very well to the drug. Her vet does not seem concerned but I am.They said they will call me when it comes in. I am concerned that the absence of this drug will cause havoc with her system. Do you agree with her vet's non concern?

My 17kg cocker was diagnosed 14 days ago with cushings ,took 30mg once a day great improvement day 7 to 10 then symptoms reappeared so acth test done and a additional dose of 30mg added 12 hours apart yesterday but noticed today her hind legs giving way and she's just lying about not interested in anything could this just be side affects of additional dose

I have a shih tzu who was diagnosed with cushings. He is getting veteryl 5mg PO QAM. He is still having symptoms of drinking a lot and barking for food and some lethargy but not as bad and one thing that is new...he does not like to lay on soft surfaces. I found a group online and one of the women had asked me to ask you...my vet suggested they compound the veteryl to 2.5 and give him one pill daily. Should he take that doseage? Or...should he take 5mg BID...do you have any advice?

She had the lab test it again to be sure. He is still drinking tons of water, he will only sleep on hard surfaces and pants more.

His liver function was better with the Denamarin and he is still taking 5 mg of veteryl. They suggested maybe compounding it to a 2.5...or a 1/4 of a prednisone tablet if he is depleted but not typically recommended.

What should I do?? You see the notes here. I do not know if I should change the dose or leave it. He is having symptoms of heavy drinking and won't sleep on soft surfaces. He also is barking again for food.....oiy!! Sorry it took so long....He started at a weight of 14.10lbs and now weigh 17lbs...

He eats royal canin so dry with science diet gastro wet. His stools are pretty normal again since starting the diet the end of sept....

My dog is 10 pound chihuahua with pituitary tumor and cushings (also hypothyroid). Diagnosed with cushings in 6 months ago and we haven't seen any improvement. Started him on 10mg, then 20mg, then 30mg. 30mg seemed to me helping up until about 3 or 4pm, so we had a compounding pharmacy make 15mg tablets. We started last week giving him 15mg morning and evening, they did nothing. Yesterday, we did 30mg am and then about 25mg in the evening and I noticed a great difference, but that seems high for a chihuahua. So first issue is how are we going to dose him and second is, he is now peeing in his kennel while I'm at work and can't hold it while I am gone. He won't pee on puppy pads, we tried that yesterday and came home to an hours worth of cleaning up pee.

My 13 year old 16 lbs Shih Tzu has Cushings Disease. After pituitary gland tumor removal in August, she has been on Trilostane. Current dose 40 mg 2 X daily. 80mg per day. She is being syringe fed 100 -120 CC Royal CanIne Recovery food. Her ACHT is now in the normal range. However, we are now seeing her have shuddering and front and hind leg collapse. Any advice? We are very concerned. Thank you so much

Hi Dr Peterson I would like your opinión please. My dog have been on vetory 30mg once a day for almost 3 months and the cortisol levels of now are normal but she still loosing hair, drinking loads, peeing everywhere, obsess with food, panting (is winter here) and she is 3 times her normal size, she really didnt improve at all but the vet says her cortisol levels are normal now so we should.not give her a higher dosis of the drug. Will she eventually be better? They did see a adrenal gland very big and 2 suspicious things (like tumors) in her liver. But they said they cant do surgery to remove it as they do now have the skill or equipement. (We are in Spain) Im desperate.

I have a French poodle 17 years old heavy 9 kg. The past 3 years has been on the treatment of Vetoryl 30 mg once a day. 2 months ago the dog was feeling ill, vomiting, loss of appetite and fatigue so we run ACTH test. It showed extremely low level of cortisol. The therapy is reduced to 15mg, repeated the test after 14 days and again was low cortisol. Therapy was reduced to 7.5 mg and the results were: after 4 hours of 20.18 nmol/l after 5 hours of 23.59 nmol/l CLIA method. In consultation with the doctor dose was reduced to 5 mg once daily, and control scheduled in 14 days. However dog began more and more to drink water and urinate in the house. Also a lot of panting and little to shake. In consultation with the doctor giving her 2 times daily 5 mg Vetroryl. I would ask for your opinion. I'm also interested why Vetroryl capsules should not be opened. We live in Serbia, where the drug is not registered and we are ordering it from abroad. It would be cheaper to order a box of 120mg and than the state pharmacy division would split and encapsulate the lower dose. Please note that in addition to her prescribed therapy I give her also Ipaktine, Flexanin I Anima Strath.Thanks in advance

Hi Dr. PetersonI have a 2.350kg mini poodle who was diagnosed with pituitary-dependent hyperadrenocorticism 1 year ago and then started treatment with trilostane 5mg once a day, with great improvement (in clinical signs and in lab tests - cortisol post acth ranges between 3 - 3.7). The vet also prescribed ACE inhibitor and amlodipine for blood pressure control. One month ago, the vet switched trilo to twice a day (last exam was normal - basal cortisol 2.2 and post ACTH 3), but changed the total dose to double (5mg twice daily – 3,4mg/kg/day). The cortisol measured after 2 weeks was basal=0.59 and post ACTH=1.57 (no clinical signs of hypoadrenocorticism). Then the vet reduce trilo to 4mg twice a day. I asked about stopping the drug and repeating ACTH stimulation test , but he thinks it's no necessary. I appreciate any advice you can give. Thanks in advance.Flavia from Brazil

Thanks for your answer, Dr. Peterson!I made a mistake in the calculation of the double dose, it was 4mg/kg/day (5mg BID and weight was 2,5kg).The current dose is 3,4 mg/kg/day (4mg twice a day and weight 2,350kg). So, you think the dose is OK?Thanks again.

My dog is a little over 16 yrs and was diagnosed with cushing about a year and a half ago and has been on Vetoryl since. He takes 30 mg once a day and has been doing great up until a few months ago. He started showing clinical signs of drinking a lot, losing fur and a huge increase in appetite towards evening. His acth tests have been great. What are your thoughts on 15 mg twice daily?

Hello Dr Peterson. This is James from 1/19/2017. We've been giving 15mg of Vetoryl since asking your opinion. His September ACTH stem results (while on 30mg am only) were 3.6 and 3.8 pre and post. On 2/23/2017 his pre and post were 2.8 and 6.4. This was an am test. Was wondering about your opinion as to whether this is an improvement or decline in numbers. Doesn't really seem to be a change in symptoms and was wondering if it is worth the cost and effort to give twice a day. Any advise you could give would be greatly appreciated. Thank you

ACTH stimulation test results aren't always the best way to evaluate the response, although the test is the best way to determine overdosage. Talk to your vet about why the clinical signs aren't improving. You might have to increase the dose further. It's always safer to give the drug twice day but if it's not working then something else could be responsible.

My dog is a 20 lb. Welsh Terrier, diagnosed with Cushing's a year ago. He has been taking Vetoryl, with dosage increasing in increments from 30 mg to currently 70mg daily. His numbers on the ACTH stimulation test have never reached normal levels. (12.8 post.) Vet is now recommending discontinuing Vetoryl instead of continuing increases in Vetoryl.

Hello Doctor,What a wonderful resource you have provided! I have a 10 year old German Shepherd that has just been officially diagnosed with Pituitary Dependent Cushing's based on the Low Dose Dexa test. Ultrasound was pretty normal except for a possible cyst on one testicle. Alk Phos is through the roof, steadily climbing over the past year or so. He has pot belly, panting, insomnia, ravenous appetite, muscle wasting, etc. I have started him on melatonin and HMR Lignans, milk thistle, as well as acupuncture which have helped a bit with the insomnia, as well improved his mood and alertness. We are about to start Trilostane, and I was wondering what starting dosage you would recommend. I intend on doing the two times daily dosing.Thanks so much!

Dr. Mark E. Peterson

About Insights into Veterinary Endocrinology

This blog is written specifically to serve veterinarians and veterinary technicians. I've divided the posts into 3 types: (1) my insights into specific endocrine issues, (2) Q & A posts that deal with questions I've gotten from veterinarians, and (3) reviews of current endocrine publications (with my comments and "insights").